Familial Hypercholesterolemia Learning In Patients With Low-density Lipoprotein Receptor And Its Ligand Gene Mutation In The Investigation

Object: To determine the molecular basis of familial hypercholesterolemia (FH) in China. Methods: 34 unrelated patients in 8 families with clinically diagnosed heterozygous FH were screened for mutations in coding and promoter region of the low density lipoprotein (LDL) receptor gene using single strand conformation polymorphism (SSCP) and DNA sequencing. Mismatch primer strategy and SSCP were used to detect apolipoprotein B (apoB) mutations. ApoE genetyping (E2, E3, E4) was carried out by gene amplification and cleavage with Hhal restriction enzyme. Results: 10 different mutations in the LDL receptor gene were indentified. All of these mutations have not been described before. No apolipoprotein B (apoB) mutations responsible for familial ligand-defective apoB-100 (FDB) were indetified. Polymorphisms of apolipoprotein E (apoE) were obersved and showed minor effects on the lipid and lipoprotein profile in FH patients. However, a significantly higher frqeuency of apoE4 genetype was found in FH patients (40%) than in those coronary heart disease patients (12.4%). Conclusion: the PCR-SSCP method is very effective to confirm information about LDL receptor gene mutations. Chinese FH patients may have specific spectrum and regional difference of LDL receptor gene mutations. Apolioprotein B-100 gene mutation might not be the main cause of FH patients in china.The increased apoE4 genetype was partly invovled in IHD in FH.